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Aim To investigate the inhibitory effect of copper gluconate and disulfiran on the PLpro of SARS-CoV-2 and to explore the effect of combination of them on PLpro.Methods SARS-CoV-2 PLpro was purified by recombinant expression technology of he effects of copper gluconate and disulfiram on PLpro activity were studied by enzyme kinetic method.Results Copper gluconate and disulfiram had high inhibitory activity on SARS-CoV-2 PLpro,Ubiquitin-7-Amino-4-methylcoumarin(Ub-AMC)was used as the fluorescent substrate.The IC50 of copper gluconate was 33.02 nmol·L-1,showing competitive inhibition,and the IC50 of disulfiram was 480.4 nmol·L-1,showing non competitive inhibition,and the combination of the two inhibitors showed the advantage of synergistic inhibition.Conclusions Copper gluconate and disulfiram have a high inhibitory effect on SARS-CoV-2 PLpro protein,and the combination shows the advantage of synergistic inhibition.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the efficacy of CD151 gene delivery in promoting blood perfusion in swines after myocardial infarction.</p><p><b>METHODS</b>Swines received coronary artery ligation and intramyocardial injection with rAAV-CD151, rAAV-anti-CD151 or rAAV-GFP. Eight weeks after vector injection, Western blot, immunostaining and 13N-labeled NH3 PET were performed to detect gene expression and biological effects of various treatments.</p><p><b>RESULTS</b>High level of CD151 protein expression was detected in the rAAV-CD151 group. The capillary density in the rAAV-CD151 group [(83.8 +/- 6.7) n/mm2] was significantly higher than that in the control group [(33.2 +/- 4.5) n/mm2] and rAAV-GFP group [(41.6 +/- 5.6) n/mm2] (all P<0.05); the arteriole density in the rAAV-CD151 group [(16.4 +/- 2.5) n/mm2] was also higher than that in the control group [(6.6 +/- 2.3) n/mm2] and the rAAV-GFP group [(8.4 +/- 1.6) n/mm2] (all P<0.05). However, the lowest capillary density and arteriole density were evidenced in rAAV-anti-CD151 group. Myocardial blood perfusion was significantly increased in rAAV-CD151 group and significantly reduced in rAAV-anti-CD151 group (all P<0.05 vs. control).</p><p><b>CONCLUSION</b>Intramyocardial injection of rAAV-CD151 could enhance the myocardial express of CD151 protein, increase capillary and arteriole densities and improve blood perfusion in swine with myocardial infarction.</p>
Subject(s)
Animals , Female , Humans , Male , Antigens, CD , Genetics , Coronary Occlusion , Therapeutics , Dependovirus , Genetics , Gene Transfer Techniques , Genetic Therapy , Genetic Vectors , Myocardial Infarction , Therapeutics , Neovascularization, Physiologic , Swine , Swine, Miniature , Tetraspanin 24 , Treatment OutcomeABSTRACT
Objective To explore the characteristic of the genetic frequency distribution of human leukocyte antigen(HLA)-DR alleles in children with bronchial asthma in Guangxi area.Methods Eighty-four unrelated asthmatic individuals and 168 healthy people without asthma and atopy living in Nanning region of Guangxi as control group were involved in the study.All asthmatics had their serum total IgE levels measured with Pharmacia UniCAP system,and skin-prick test with 10 kinds of inhalant allergens were taken,and pulmonary function were measured among the asthmatic.HLA oligonucleotide array was used to 21 gene frequencies of HLA-DR.Results The frequencies of HLA-DR B1*070X allele and HLA-DR B1*11XX allele among the asthmatic(2.98% and 13.69%)were significantly higher than those in control group(0.3% and 5.95%)(?2 =6.915,9.478 P
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The objective of this study was to investigate the effects of the aromatase inhibitor (AI) letrozole on gonadal development, serum steroids and aromatase activities in 2-year-old female red spotted grouper (Epinephelus akaara) during reproductive season. Groupers were divided into two groups, one implanted with aromatase inhibitor (AI, 5 mg/kg body weight) and the other elastomer without AI into peritoneal cavity once every four weeks for 8 weeks. Spermiation was checked through gentle abdominal pressure every 2 weeks. Blood samples were obtained from 6 fish of each group every 4 weeks for later analysis of sex steroids. After blood samples were collected, forebrain, midbrain, hindbrain, and gonads were collected and stored at -70 degrees C for later aromatase activity measurement and gonadal histological study. Significantly lower gondadosomatic index (GSI) was observed in AI-implanted group. Fish implanted with AI once showed complete degradation of oocytes and sex inversion with developing testicular tissues in the 4th week. AI induced females to develop into functional males with authentic males testes similar in structure to those in normal males. Spermiating rate of AI-treated males were 14.3%, 35.3%, and 48.4%in the 4th, 6th, and 8th week, respectively, while all fish in the control group were still female with developing ovaries. Aromatase activities in gonads decreased significantly after implantation with aromatase inhibitor, but showed no significant difference between control and AI-implanted group. No difference in serum testosterone (T) levels was observed in control and AI-treated group, while serum levels of 17beta-estradiol (E(2)) decreased but 11-ketotestosterone (11-KT) concentration increased significantly. The present results suggest that the decrease in serum 17beta-estradiol (E(2)) and increase in 11-KT levels may be important for sex inversion induced by aromatase inhibitor in red spotted grouper.
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Objective To explore the association between the characteristics of the genetic polymorphism of human leukocyte antigen (HLA)-B and HLA-DR alleles and asthma in Guangxi Zhuang and Han nationality children.Methods Eighty-four blood-unrelated asthmatic individuals,57 cases of Han nationality and 27 cases of Zhuang children with asthma,and 168 healthy controls,included 83 cases of Han nationality and 85 cases of Zhuang people without asthma and atopy living in Nanning region of Guangxi were involved in the study.All asthmatic patients′serum total IgE levels were measured with UniCAP Pharmacia system,and skin-prick test with ten kinds of inhalant allergens were taken and pulmonary functions were measured among the patients.HLA oligonucleotide array was used to 40 gene alleles of HLA-B and 26 HLA-DR.Comparison of the frequency distribution of HLA-DR alleles and HLA-B alleles in 2 groups was evaluated by chi-square test,and the risk for asthma of the HLA allele′s carriers was valuated by OR value.Results Twenty-seven alleles at HLA-B locus and 21 alleles at HLA-DR were detected.The distribution of HLA-B46,HLA-DRB1070X and HLA-DRB111XX alleles only in Han people was distinctive in the asthmatic patients compared with those in healthy controls(Pa